Genetic variation linked to liver cirrhosis in alcoholic Caucasians identifiedDecember 17th, 2010 - 2:27 pm ICT by ANI
Washington, Dec 17 (ANI): A variation in the PNPLA3 (adiponutrin) gene is associated with cirrhosis of the liver and elevated transaminase (liver enzyme) levels in alcoholic Caucasians, a new study by German researchers has found.
The risk of cirrhosis in alcoholics in the genetic high-risk group might be as high as 25 pc to 50 pc.
Alcoholic liver disease (ALD)-ranging from alcoholic fatty liver to alcohol induced liver fibrosis and cirrhosis-accounts for more than 50pc all chronic liver disease in industrialized countries.
Studies have shown that while all heavy drinkers display signs of hepatitis steatosis (fatty liver), only 10 pc to 35 pc of alcoholics develop hepatic inflammation, with up to 20 pc progressing to cirrhosis. Further medical evidence suggests a link between PNPLA3 gene variation and liver fat content; specifically the single nucleotide polymorphism (SNP) rs738409 was reported previously to be associated with advanced alcoholic liver disease in alcohol-dependent individuals of European and Native American descent.
The German research team led by Jochen Hampe, from Christian-Albrechts-Universitat Kiel determined the genotype and allele frequencies of PNPLA3 rs738409 in 1043 alcoholics with or without alcoholic liver injury and in 376 at-risk drinkers from a population-based cohort. Cirrhosis and steatosis was determined by liver biopsy and standard diagnostic testing. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were established using routine clinical chemistry testing.
Participants were categorized as alcoholic liver cirrhosis (ALC); alcoholics with liver steatosis on ultrasound and elevation of ALT as alcoholic liver damage (ALD); alcoholic liver steatosis and normal liver enzyme levels as alcoholic fatty liver (AFL); and alcoholics with normal appearance of the liver on ultrasound and normal liver enzyme levels as alcoholic controls.
Researchers discovered that SNP rs738409 was strongly over-represented in patients with ALC and ALD compared to alcoholics without liver damage. Additionally, the frequency of allele PNPLA3 rs738409 in AFL participants was lower than in alcoholics without steatosis and normal liver enzymes.
“Our findings show PNPLA3 rs738409 carriers represent a subpopulation
of high risk individuals susceptible to progression from clinically silent alcoholic liver disease to obvious cirrhosis,” Dr. Hampe concluded.
“Carriers of this risk allele should be targeted for future pharmaceutical treatments and non-pharmacological interventions.”
Full findings have been published in the January 2011 issue of Hepatology, a journal of the American Association for the Study of Liver Diseases. (ANI)
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